Back to the Top
The statements below are from the recent EMEA attempt at defining stability in validations.line 262 to 269
Stability should be ensured for every step in the analytical method, meaning that the conditions applied to the stability tests, such as sample matrix, materials storage and analytical conditions should be similar to those used for the actual study samples. Stability cannot be proven by literature data.
Stability of the analyte and IS in the studied matrix is evaluated using at least triplicates samples of the low and high QC samples which are analysed immediately after preparation and after the applied storage conditions that are to be evaluated. The QC samples are analysed against a calibration curve, obtained from freshly prepared calibration standards, and the obtained concentrations ( for each QC sample??) are compared to the nominal concentrations. The deviation should be within +/-15%.
Does this indicate how the measurements are used? For the three QCs at each level do we take the mean of the three samples or do we look at each sample's return value and use the deviation from the individual values to determine if the sample is acceptable, and is a minimum of 2/3 passing at each level needed before claiming stability?
The instructions from the 2001 guidance are equally obscure, below:
3. Long-Term Stability
The storage time in a long-term stability evaluation should exceed the time between the
date of first sample collection and the date of last sample analysis. Long-term stability
should be determined by storing at least three aliquots of each of the low and high
concentrations under the same conditions as the study samples. The volume of samples
should be sufficient for analysis on three separate occasions. The concentrations of all (each??)
the stability samples should be compared to the mean of back-calculated values for the
standards at the appropriate concentrations from the first day of long-term stability
Again is it the mean or the individual values? If it is the mean of three that is taken it is possible for two of the individual values to fail accuracy but for the three to pass precision and accuracy for the timepoint. IF two of my values did not meet accuracy I would not accept the mean as passing. Appreciate your comments
-- Edward F. O'Connor
78 Marbern Drive
Suffield, Ct 06078-1533
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Stability Validation" as the subject
Support PharmPK by using the
Copyright 1995-2011 David W. A. Bourne (email@example.com)